The work proposed will continue the study of factors protecting the stomach from damage by its own secretions and of the pathophysiological responses of the stomach when the protective mechanisms fail. The lines of work will be the following. (1) Permeability of gastric mucosal capillaries to plasma proteins and the turnover of plasma proteins between plasma and gastric interstitial space will be measured whrn the stomach is at rest, when it is stimulated to sectete and when it is damaged. Damage iwll include conditions leading to protein-losing gastropathy. (2) Mucosal permeability to large molecules will be studied. This study will include attempts to trace pathways by means of electronmicroscopic observations of the fate of intra-arterially injected horseradish peroxidase and other large, detectable molecules. (3) Mucosal permeability to small molecules will be studied with particular reference to developing techniques for detecting whether the gastric mucosal barrier can be strengthened and the back-diffusion of acid into the mucosa reduced. (4) The effects of chronic damage will be studied to assess the factors affecting the mucosa's ability to repair itself. Included in this will be the role of cell regeneration and the synthesis of mucus. Perhaps it will be possible to study gastric mucosal hyperplasia and hypertrophy. (5) Attempts will be made to assess the role of 5-hydroxytryptamine and kinins in the response of the mucosa to damage.